rs138442805

Positions:

• chr20-8740457-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_015192.4(PLCB1):​c.2413+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,471,662 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0090 (11 hom., cov: 32)
  • Exomes 𝑓: 0.013 (130 hom.)
• Consequence: PLCB1 NM_015192.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.582

Genes affected

PLCB1 (HGNC:15917): (phospholipase C beta 1) The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of many extracellular signals. This gene is activated by two G-protein alpha subunits, alpha-q and alpha-11. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 20-8740457-C-T is Benign according to our data. Variant chr20-8740457-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 129907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-8740457-C-T is described in Lovd as [Benign]. Variant chr20-8740457-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00899 (1369/152270) while in subpopulation NFE AF= 0.016 (1091/68026). AF 95% confidence interval is 0.0152. There are 11 homozygotes in gnomad4. There are 604 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCB1	NM_015192.4	c.2413+9C>T		intron_variant		ENST00000338037.11	NP_056007.1
PLCB1	NM_182734.3	c.2413+9C>T		intron_variant			NP_877398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCB1	ENST00000338037.11	c.2413+9C>T		intron_variant		1	NM_015192.4	ENSP00000338185	P1

Frequencies

GnomAD3 genomes AF: 0.00900 AC: 1370 AN: 152152 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00596

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00349

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0161

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00920 AC: 1937 AN: 210542 Hom.: 19 AF XY: 0.00912 AC XY: 1050 AN XY: 115146

Gnomad AFR exome AF: 0.00261

Gnomad AMR exome AF: 0.00285

Gnomad ASJ exome AF: 0.00896

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00122

Gnomad FIN exome AF: 0.00365

Gnomad NFE exome AF: 0.0158

Gnomad OTH exome AF: 0.00945

GnomAD4 exome AF: 0.0133 AC: 17530 AN: 1319392 Hom.: 130 Cov.: 19 AF XY: 0.0129 AC XY: 8507 AN XY: 661020

Gnomad4 AFR exome AF: 0.00197

Gnomad4 AMR exome AF: 0.00387

Gnomad4 ASJ exome AF: 0.00873

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00107

Gnomad4 FIN exome AF: 0.00496

Gnomad4 NFE exome AF: 0.0160

Gnomad4 OTH exome AF: 0.0126

GnomAD4 genome AF: 0.00899 AC: 1369 AN: 152270 Hom.: 11 Cov.: 32 AF XY: 0.00811 AC XY: 604 AN XY: 74454

Gnomad4 AFR AF: 0.00217

Gnomad4 AMR AF: 0.00595

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00349

Gnomad4 NFE AF: 0.0160

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.0129 Hom.: 9

Bravo AF: 0.00942

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 29, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 15, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Developmental and epileptic encephalopathy, 12 Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 16, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.5
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs138442805; hg19: chr20-8721104;